We wish to define the etiology of Crohn's disease, in particular, the role of the transmissible agent in causing this disease. The objectives are: (1) to use athymic mice (nu/nu) to study the putative transmissible agent, (2) to isolate and characterize the putative agent from human and nu/nu tissue. Using nu/nu, our initial studies are unexpected and exciting, Crohn's disease lymph node homogenate from 9 different patients induced malignant lymphoma in nu/nu whereas control lymph node homogenated did not. Electron microscopic examination of the tumors and one lymph node homogenate from a patient with Crohn's disease showed presence of virus particles by thin sectioning and negative staining with phosphotungstic acid. Two lymphomas ae being cultured in vitro and both of them are B cell lymphoma. We intend to extend these observations using a large number of nu/nu to examine the reproducibility, specificity, effect of dosage of the materials injected, and to culture the lymphomas both in vivo and in vitro. We will also study antigenic recognition in the lymphoma and other internal organs of the nu/nu (e.g., liver, spleen, intestine) using immunofluorescent techniques and appropriately absorbed sera from patients with Crohn's disease and control subjects. Similar recognition will be investigated in established lymphoid cell lines from nu/nu lymphomas. Replication of the virus will be examined using co-cultivation techniques with established cell lines (e.g., WI-38 and lymphoid cells). Both human and animal tissue will be examined by electron microscopy for detection of specific virus by conventional methods and negative staining. Further characterization of the virus will be performed by plaque, enzymatic and radiolabelling assays.